AMX0035 Approved for ALS Treatment in Canada

The approval was based on phase 2/3 findings that showed an average score of 2.32 points higher on ALS Functional Rating Scale with AMX0035 compared with placebo.

According to a new announcement, Health Canada has approved AMX0035 (Amylyx Pharmaceuticals), marketed as Albrioza, for the treatment of patients with amyotrophic lateral sclerosis (ALS), marking it the first new therapy for the disease approved in Canada since 2018.1

AMX0035 was approved under Health Canada’s Notice of Compliance with Conditions (NOC/c) policy, which insinuates that the company will need to provide data from the ongoing phase 3 PHOENIX study (NCT05021536) to uphold its approved conditions. The medication is still under review with the FDA, with a decision now expected to come in September 2022, rather than at the end of June.2

"For nearly a decade, we have been committed to creating more meaningful moments for people living with ALS and their families. We are excited with Health Canada’s decision to approve Albrioza with conditions," Justin Klee and Joshua Cohen, co-CEOs, and co-founders, Amylyx, said in a statement.1 "Albrioza is a therapy that demonstrated in our CENTAUR trial a statistically significant and clinically meaningful impact on function, alone or in addition to existing ALS therapies.”

AMX0035, an orally administered fixed-dose coformulation of sodium phenylbutyrate-taurursodiol, was approved based on data from the phase 2/3 CENTAUR study (NCT93127514) and its open-label extension study. Patients were randomized 2:1 to either AMX0035 or matching placebo, administered twice daily by mouth or feeding tube for a planned duration of 24 weeks. The investigational agent met its primary end point, with a reported average ALS Functional Rating Scale-Revised (ALSFRS-R) score of 2.32 points higher than placebo (P = .03) at the end of the analysis.

Additional survival data, released in October 2020, demonstrated a median survival of 25 months (95% CI, 19.0-33.6) for those on study drug compared with a median survival of 18.5 months in the placebo group (95% CI, 13.5-23.2) for an HR of 0.56 (95% CI, 0.34-0.92; = .023), equating to a 44% lower risk of death. Furthermore, at 1 year, the estimated probability of survival was 80.9% (95% CI, 71.1-87.7) for the AMX0035 group compared to 72.9% for those on placebo (95% CI, 58.0-83.3). For 2 years, the estimates were 51.6% (95% CI, 38.9-62.9) and 33.9% (19.4-49.1), respectively.3

"We are delighted that this Health Canada approval represents the advancement in available treatment options for people living with ALS, but there is still more work to be done,” Tammy Moore, chief executive officer, ALS Society of Canada, said in a statement.1 "ALS is a devastating disease and can move with startling swiftness. It is incredibly important that all Canadians across the country are able to benefit from these and other innovations to come, as quickly as possible following regulatory approval. We are hopeful that decision-makers throughout the drug access and reimbursement process will work expeditiously to provide timely and equitable access for all Canadians who may benefit. There is simply no time to wait with this disease."

PHOENIX, the ongoing 48-week, randomized, placebo-controlled trial assessing AMX0035, is expected to have data read out in 2024. With an estimated enrollment of 600 participants with definite or clinically probable ALS within 24 months of symptom onset, the study will also use ALSFRS-R as the primary outcome, along with survival.

In March 2022, in the United States, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted that the current data on AMX0035 were not sufficient in demonstrating efficacy. The committee voted 6—4 (6 no; 4 yes; 0 abstain) that the data from CENTAUR and the open-label extension did not adequately establish the therapeutic as an effective treatment for ALS. Several of the AdComm members who voted against the drug had concerns over the trial’s conduct and robustness of the data, while others expressed belief that PHOENIX would help answer some of the lingering questions.4

REFERENCES
1. Amylyx Pharmaceuticals announces Health Canada approval of Albrioza for the treatment of ALS. News release. June 13, 2022. Accessed June 13, 2022. https://www.amylyx.com/media/amylyx-pharmaceuticals-announces-health-canada-approval-of-albriozatm-for-the-treatment-of-als
2. Amylyx Pharmaceuticals Receives Notification of PDUFA Date Extension for AMX0035 for the Treatment of ALS. News release. Amylyx. June 3, 2022. Accessed June 13, 2022. https://finance.yahoo.com/news/amylyx-pharmaceuticals-receives-notification-pdufa-110000354.html
3. Paganoni S, Hendrix S, Dickson SP, et al. Long‐Term Survival of Participants in the CENTAUR Trial of Sodium Phenylbutyrate‐Taurursodiol in ALS. Muscle Nerve. Published online October 16, 2020. doi: 10.1002/mus.27091.
4. FDA. Peripheral and Central Nervous System Drugs Advisory Committee Meeting. March 30, 2022. Accessed June 13, 2022.